Chronic administration of opiates produces a dependent state which is generally characterized by abstinence behavior when opiate intake is abruptly terminated or when an opiate antagonist is administered. Recently, a number of investigators have shown that fragments of beta-lipotropin (LPH) have opiate agonist activities when bioassayed in mouse vas deferens, guinea pig ileum or stereo-specific binding to purified brain extracts. Of the active lipotropin fragments, we have shown that beta-endorphin (LPH 61-91) in particular, is a potent analgesic agent. In comparing the pharmacological properties of opiate-like peptides to opiate alkaloids, it is of importance to know if these peptides can cause physical dependence. The development of a novel technique of drug delivery, the osmotic minipump system, has enabled me to show that chronic exposure to methionine-enkephalin and beta-endorphin can result in physical dependence. In the past year, I have completed studies which: (1) Compared the behavioral and cardiovascular effects of beta-endorphin, enkephalin analogs, and morphine. (2) Established the basic conditions for using the osmotic minipump technique in the bioassay of the potency of opioid peptides for producing physical dependence. (3) Showed that the agonist potency of an opiate or opioid peptide is inevitably correlated to potency for producing physical dependence. (4) Determined the brain sites where physical dependence develops after chronic infusion of opiates into localized brain regions.